Preventing the sexual transmission of HIV is essential if the United States is to further reduce HIV incidence. Among drug-using populations, however, the sexual transmission of HIV is understudied. The proposed five-year study focuses on injection drug users (IDUs) and drug-using men who have sex with men (MSM) to examine the sexual diffusion of HIV within and across drug-using population subgroups and to non-drug using and non-MSM populations. Our approach combines 1) behavioral epidemiology, 2) two-types of social network analyses with strong geographic mapping components [including the ability to link geographic location with local socio-economic and health data], 3) mathematical modeling, and 4) and biologic testing for HIV, hepatitis B (HBV) and C (HCV), syphilis, chlamydia and gonorrhea. The study proposes a cross sectional survey of 2500 IDUs and about 562 of their non-injecting sex partners, and 3000 MSM and about 450 of their female sex partners. Participants will be recruited through respondent-driven sampling (RDS) [1-3] at six racially and ethnically diverse sites across Chicago. As a feature of RDS, sampling weights will be calculated to adjust for unequal probabilities of selection based on variations in network size, strength of in-group affiliation and recruitment effectiveness, and the data will be post-stratified so the results can be generalized to the population of IDUs and drug-using MSM. HIV specimens from participants with newly diagnosed infections will be tested using the serologic testing algorithm for recent HIV seroconversion (STARHS), and HIV incidence computed from the results. HIV genotyping and phenotyping, RNA viral load testing, and cellular immune panels will be used to characterize newly diagnosed infections by drug resistance, infectiousness, and immune system suppression. Test results for other STIs will be used to better characterize the potential for future diffusion of HIV or increased vulnerability to infection with HIV.